The long term objective of this proposal is a better understanding of the ways in which the production of blood platelets is regulated. It is well known that the level of platelets in the blood regulates megakaryocytopoiesis, but there is an increasing amount of evidence that megakaryocytes are probably also regulated by other factors. The hypothesis being tested in the proposed experiments is that the number of megakaryocytes themselves may, in part, regulate megakaryocytopoiesis. Conditions characterized by megakaryocytopenia with normal (or disproportionately high) platelet production will be studied and compared with experimentally induced thrombocytopenia with intact marrow and also conditions in which both megakaryocytes and platelets are low. Measurements will be made of megakaryocyte size, DNA content, and number, total marrow cells, and blood platelets, red cells, and white cells. Liquid cultures of marrow cells will be done to detect abnormalities of hemopoietic stromal cells. Megakaryocyte colony-forming cells will be measured in an effort to evaluate their physiological role in vivo.